Effect of bone marrow mesenchymal stem cells via portal vein injection on transforming growth factor-βR1 and -βR2 in rats with acute liver failure_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

XU Tubing ¹ , LI Li ² , MU Hanzheng ² ,  LUO Xingdi ² , SHUAI Ling ³ , ZHANG Yujun ³

1. Department of General Surgery, The Sixteenth Hospital of PLA, Aletai, Xinjiang Uygur Autonomous Region 836500, P.R.China;
2. Medical Affair, The Sixteenth Hospital of PLA, Aletai, Xinjiang Uygur Autonomous Region 836500, P.R.China;
3. Institute of Hepatobiliary Surgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, P.R.China;

Corresponding author：

LUO Xingdi, Email: 750711050@qq.com

Keywords：

bone marrow mesenchymal stem cell; transforming growth factor-β receptor 1; transforming growth factor-β receptor 2; acute liver failure; rat

DOI：

10.7507/1007-9424.201612081

Video：

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Objective To investigate effect of bone marrow mesenchymal stem cells (BMSCs) via portal vein injection on transforming growth factor-β receptor 1 (TGF-βR1) and TGF-βR2 in rats with acute liver failure (ALF). Methods Sixty male SD rats were randomly divided into a normal control group, ALF model group, and BMSCs treatment group, with 20 rats in each group. The rats of normal control group were directly sacrificed without other treatment. The ALF models were made in the rats of BMSCs treatment group and ALF model group, then were treated with BMSCs and equal volume of normal saline respectively. On day 7 after treatment, the 1-week survival situation of rats was observed, the pathological change was observed by HE staining, the apoptosis of liver cells was detected by TUNEL method, and the TGF-βR1 and TGF-βR2 proteins expressions were detected by Western blot method. Results ① The 1-week survival rate of the BMSCs treatment group was significantly higher than that of the ALF model group (P<0.05). ② In the ALF model group, the liver cells were diffuse necrosis, the lobular structure was indistinct, and a large number of bridging necrosis. In the BMSCs treatment group, the infiltrations of inflammatory cells were decreased, and the structure of hepatic lobules gradually recovered, and the normal hepatocytes were seen around it. ③ The apoptosis indexes of the BMSCs treatment group and the ALF model group were significantly higher than those in the normal control group (P<0.05), which in the BMSCs treatment group was significantly lower than that of the ALF model group (P<0.05). ④ The TGF-βR1 and TGF-βR2 proteins expressions in the liver tissues of the ALF model group were significantly higher than those of the normal control group (P<0.05), which of the BMSCs treatment group were significantly lower than those of the ALF model group (P<0.05). Conclusion BMSCs could inhibit apoptosis of hepatocytes in ALF. Its mechanism might be related to expressions of TGF-βR1 and TGF-βR1 proteins, but its specific regulatory pathway needs to be further studied.

Citation： XU Tubing, LI Li, MU Hanzheng, LUO Xingdi, SHUAI Ling, ZHANG Yujun. Effect of bone marrow mesenchymal stem cells via portal vein injection on transforming growth factor-βR1 and -βR2 in rats with acute liver failure. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2017, 24(8): 953-957. doi: 10.7507/1007-9424.201612081 Copy

1.	Bajaj JS, O’Leary JG, Reddy KR, et al. Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures. Hepatology, 2014, 60(1): 250-256.
2.	Karvellas CJ, Todd Stravitz R, Battenhouse H, et al. Therapeutic hypothermia in acute liver failure: a multicenter retrospective cohort analysis. Liver Transpl, 2015, 21(1): 4-12.
3.	Butterworth RF. Pathogenesis of hepatic encephalopathy and brain edema in acute liver failure. J Clin Exp Hepatol, 2015, 5(Suppl 1): S96-S103.
4.	Romero-Gómez M, Montagnese S, Jalan R. Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure. J Hepatol, 2015, 62(2): 437-447.
5.	王香梅. 拉米夫定与恩替卡韦治疗慢性乙型肝炎慢加亚急性肝衰竭的临床研究. 中国临床研究, 2014, 27(3): 297-298.
6.	郭会敏, 李颖, 朱彦涛, 等. 36 例人工肝胆红素吸附治疗肝衰竭病人的护理. 护理研究, 2015, 29(7): 2423-2424.
7.	张美华, 余卫, 王巧瑜, 等. 骨髓间充质干细胞治疗大鼠白毒伞中毒致急性肝衰竭的效果. 广东医学, 2016, 37(13): 1917-1920.
8.	Robles-Diaz M, Lucena MI, Kaplowitz N, et al. Use of Hy’s law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury. Gastroenterology, 2014, 147(1): 109-118. e5.
9.	Karkhanis J, Verna EC, Chang MS, et al. Steroid use in acute liver failure. Hepatology, 2014, 59(2): 612-621.
10.	Li H, Xia Q, Zeng B, et al. Submassive hepatic necrosis distinguishes HBV-associated acute on chronic liver failure from cirrhotic patients with acute decompensation. J Hepatol, 2015, 63(1): 50-59.
11.	Feng T, Zhang J, Zeng G, et al. Therapeutic potential of umbilical cord mesenchymal stem cells in mice with acute hepatic failure. Int J Artif Organs, 2015, 38(5): 271-276.
12.	李小鹏, 张伦理. 慢加急性肝衰竭研究新进展. 内科急危重症杂志, 2014, 20(3): 157-158.
13.	李晓东. HBV 相关慢加急性肝衰竭免疫病理发病机制研究进展. 实用肝脏病杂志, 2015, 18(3): 317-320.
14.	刘海霞, 朱跃科, 孟庆华. 慢加急性肝衰竭的定义、病理生理学基础和临床管理. 临床肝胆病杂志, 2016, 32(9): 1684-1687.
15.	贾琳, 李娟, 朱跃科, 等. 乙型肝炎相关慢加急性肝衰竭患者外周血树突状细胞水平及临床意义. 临床肝胆病杂志, 2015, 31(5): 711-715.
16.	卢新军, 陈颖华, 马毅, 等. 原位肝移植术后耐激素性急性排斥反应的临床诊治策略. 中华肝脏病杂志, 2016, 24(4): 297-301.
17.	白建华, 陈刚, 朱新锋, 等. 原位肝移植模型的建立技巧与改进. 中国组织工程研究, 2015, 19(40): 6526-6530.
18.	吴婧, 倪鎏达. 急性肝衰竭预后评估模型的研究近况. 肝脏, 2015, 24(3): 248-250.
19.	裴利娟, 徐鸿滨, 金鑫, 等. 急性肝功能衰竭急诊肝移植围术期治疗的单中心经验探讨. 中国组织工程研究, 2014, 18(36): 5741-5746.
20.	崔丽娜, 韩英. 多能干细胞在肝脏损伤和修复过程中的免疫调节作用. 临床肝胆病杂志, 2014, 30(9): 855-859.
21.	宋囡, 何文智, 王智民, 等. 骨髓间充质干细胞在骨向分化的作用及中医药研究进展. 中国骨质疏松杂志, 2014, 20(1): 95-99.
22.	李志超, 杨海杰, 剧飞, 等. TGF-β1 通过激活 Smad 信号途径抑制 PI3K/AKT 信号介导的 BMSC 成脂分化. 中国生物化学与分子生物学报, 2015, 31(10): 1077-1084.
23.	郑盛, 杨涓, 张帆, 等. 骨髓间充质干细胞移植对急性肝功能衰竭大鼠血清及肝组织 HMGB1 表达的影响. 中华器官移植杂志, 2015, 36(12): 714-719.
24.	王海燕, 何创, 肖建斌, 等. 转化生长因子-β-1 抗体对肺损伤纤维化大鼠细胞外基质重建紊乱的调控. 医学研究生学报, 2014, 24(4): 368-372.
25.	符培亮, 丛锐军, 张雷, 等. 体外条件下 TGF-β3、BMP-2 和 DEX 诱导兔滑膜间充质干细胞向软骨细胞谱系分化的研究. 中国骨与关节杂志, 2014, 13(2): 135-141.
26.	靳艳文, 叶辉, 熊先泽, 等. PPARγ 激动剂拮抗 TGF-β1 介导的胆管纤维化的初步研究. 中国普外基础与临床杂志, 2016, 23(7): 790-793.
27.	曲心宇, 胡孝海, 刘君, 等. 血清 TGF-β1 和 IL-23 在胃癌诊断中的临床应用价值. 中国普外基础与临床杂志, 2016, 23(7): 818-821.

1. Bajaj JS, O’Leary JG, Reddy KR, et al. Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures. Hepatology, 2014, 60(1): 250-256.
2. Karvellas CJ, Todd Stravitz R, Battenhouse H, et al. Therapeutic hypothermia in acute liver failure: a multicenter retrospective cohort analysis. Liver Transpl, 2015, 21(1): 4-12.
3. Butterworth RF. Pathogenesis of hepatic encephalopathy and brain edema in acute liver failure. J Clin Exp Hepatol, 2015, 5(Suppl 1): S96-S103.
4. Romero-Gómez M, Montagnese S, Jalan R. Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure. J Hepatol, 2015, 62(2): 437-447.
5. 王香梅. 拉米夫定与恩替卡韦治疗慢性乙型肝炎慢加亚急性肝衰竭的临床研究. 中国临床研究, 2014, 27(3): 297-298.
6. 郭会敏, 李颖, 朱彦涛, 等. 36 例人工肝胆红素吸附治疗肝衰竭病人的护理. 护理研究, 2015, 29(7): 2423-2424.
7. 张美华, 余卫, 王巧瑜, 等. 骨髓间充质干细胞治疗大鼠白毒伞中毒致急性肝衰竭的效果. 广东医学, 2016, 37(13): 1917-1920.
8. Robles-Diaz M, Lucena MI, Kaplowitz N, et al. Use of Hy’s law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury. Gastroenterology, 2014, 147(1): 109-118. e5.
9. Karkhanis J, Verna EC, Chang MS, et al. Steroid use in acute liver failure. Hepatology, 2014, 59(2): 612-621.
10. Li H, Xia Q, Zeng B, et al. Submassive hepatic necrosis distinguishes HBV-associated acute on chronic liver failure from cirrhotic patients with acute decompensation. J Hepatol, 2015, 63(1): 50-59.
11. Feng T, Zhang J, Zeng G, et al. Therapeutic potential of umbilical cord mesenchymal stem cells in mice with acute hepatic failure. Int J Artif Organs, 2015, 38(5): 271-276.
12. 李小鹏, 张伦理. 慢加急性肝衰竭研究新进展. 内科急危重症杂志, 2014, 20(3): 157-158.
13. 李晓东. HBV 相关慢加急性肝衰竭免疫病理发病机制研究进展. 实用肝脏病杂志, 2015, 18(3): 317-320.
14. 刘海霞, 朱跃科, 孟庆华. 慢加急性肝衰竭的定义、病理生理学基础和临床管理. 临床肝胆病杂志, 2016, 32(9): 1684-1687.
15. 贾琳, 李娟, 朱跃科, 等. 乙型肝炎相关慢加急性肝衰竭患者外周血树突状细胞水平及临床意义. 临床肝胆病杂志, 2015, 31(5): 711-715.
16. 卢新军, 陈颖华, 马毅, 等. 原位肝移植术后耐激素性急性排斥反应的临床诊治策略. 中华肝脏病杂志, 2016, 24(4): 297-301.
17. 白建华, 陈刚, 朱新锋, 等. 原位肝移植模型的建立技巧与改进. 中国组织工程研究, 2015, 19(40): 6526-6530.
18. 吴婧, 倪鎏达. 急性肝衰竭预后评估模型的研究近况. 肝脏, 2015, 24(3): 248-250.
19. 裴利娟, 徐鸿滨, 金鑫, 等. 急性肝功能衰竭急诊肝移植围术期治疗的单中心经验探讨. 中国组织工程研究, 2014, 18(36): 5741-5746.
20. 崔丽娜, 韩英. 多能干细胞在肝脏损伤和修复过程中的免疫调节作用. 临床肝胆病杂志, 2014, 30(9): 855-859.
21. 宋囡, 何文智, 王智民, 等. 骨髓间充质干细胞在骨向分化的作用及中医药研究进展. 中国骨质疏松杂志, 2014, 20(1): 95-99.
22. 李志超, 杨海杰, 剧飞, 等. TGF-β1 通过激活 Smad 信号途径抑制 PI3K/AKT 信号介导的 BMSC 成脂分化. 中国生物化学与分子生物学报, 2015, 31(10): 1077-1084.
23. 郑盛, 杨涓, 张帆, 等. 骨髓间充质干细胞移植对急性肝功能衰竭大鼠血清及肝组织 HMGB1 表达的影响. 中华器官移植杂志, 2015, 36(12): 714-719.
24. 王海燕, 何创, 肖建斌, 等. 转化生长因子-β-1 抗体对肺损伤纤维化大鼠细胞外基质重建紊乱的调控. 医学研究生学报, 2014, 24(4): 368-372.
25. 符培亮, 丛锐军, 张雷, 等. 体外条件下 TGF-β3、BMP-2 和 DEX 诱导兔滑膜间充质干细胞向软骨细胞谱系分化的研究. 中国骨与关节杂志, 2014, 13(2): 135-141.
26. 靳艳文, 叶辉, 熊先泽, 等. PPARγ 激动剂拮抗 TGF-β1 介导的胆管纤维化的初步研究. 中国普外基础与临床杂志, 2016, 23(7): 790-793.
27. 曲心宇, 胡孝海, 刘君, 等. 血清 TGF-β1 和 IL-23 在胃癌诊断中的临床应用价值. 中国普外基础与临床杂志, 2016, 23(7): 818-821.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of bone marrow mesenchymal stem cells via portal vein injection on transforming growth factor-βR1 and -βR2 in rats with acute liver failure

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